Objective To investigate the Resistance of Enterobacter cloacae (EC) and risk factors of infection with multidrug resistant Enterobacter cloacae (MREC) in respiratory tract of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods A total of 96 EC were isolated from the respiratory tract of patients with AECOPD. The drug sensitivity of EC was determined by automatic microbial analyzer. The AmpC enzyme was detected by enzyme extract threedimensional test. The distribution of EC, MREC and AmpC enzyme positive EC in all grade of COPD was analyzed. The risk factors of MREC infection were analyzed by multivariate logistic regression. Results MREC accounted for 333% (32 strains). The drug resistance rates of amikacin, ceftazidime, cmpound slfamethoxazole ganules, levofloxacin, tetracycline and chloramphenicol in MREC group were significantly higher than those in drug resistant group (P all＜0.05). The detection rate of AmpC enzyme was 292% (28 strains). The resistance rate of AmpC enzyme positive EC to ceftazidime, levofloxacin and chloramphenicol were higher than those of AmpC enzyme negative EC (Pall ＜0.05). The proportion of AmpC enzyme positive EC, MREC, AmpC enzyme EC positive+ MREC in COPD of grade I~II was significantly lower than those of grade III~IV (P＜ all 0.05). Multivariate logistic regression analysis showed that the P values of "AmpC positive", " extended spectrum βlactamase positive" and "COPD clinical severity grade≥grade III" were all lower than 0.05. Conclusion The drug resistance of EC in patients with AECOPD is serious, especially in MREC and AmpC positive EC. All kinds of EC mainly infect patients with COPD clinical severity grade≥Ⅲ. The independent risk factors of MREC infection in AECOPD patients were "AmpC positive", "ESBLs positive" and "COPD clinical severity grade≥grade III".